IL-6 Promotes the Proliferation and Immunosuppressive Function of Myeloid-Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer

Biomed Res Int. 2021 Apr 23:2021:5535578. doi: 10.1155/2021/5535578. eCollection 2021.

Abstract

Muscle-invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin-6 (IL-6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL-6 and the number of myeloid-derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL-6, could significantly lower the proliferation ability of CD4+ or CD8+ T lymphocytes. Further, this study demonstrated that IL-6 could upregulate the mitogen-activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL-6 on MDSCs. These data suggested that IL-6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / physiology
  • Humans
  • Interleukin-6 / metabolism*
  • Mice
  • Middle Aged
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myeloid-Derived Suppressor Cells* / immunology
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Signal Transduction / physiology
  • Urinary Bladder / chemistry
  • Urinary Bladder / metabolism
  • Urinary Bladder Neoplasms* / immunology
  • Urinary Bladder Neoplasms* / metabolism
  • Urinary Bladder Neoplasms* / mortality

Substances

  • IL6 protein, human
  • Interleukin-6
  • interleukin-6, mouse
  • Mitogen-Activated Protein Kinases